CN116322875A

CN116322875A - Oral drug delivery device with expansion arm

Info

Publication number: CN116322875A
Application number: CN202180063363.8A
Authority: CN
Inventors: M·F-M·巴尔森; M·K·福德汉姆; J·A·霍恩斯比; N·S·瓦西拉基斯; S·L·克拉克
Original assignee: Eli Lilly and Co
Current assignee: Eli Lilly and Co
Priority date: 2020-09-16
Filing date: 2021-09-15
Publication date: 2023-06-23
Also published as: AU2021343442A1; EP4213806A2; CA3192421A1; AU2021343442B2; WO2022060817A2; US20230381098A1; WO2022060817A3; JP2023541659A

Abstract

The present disclosure provides a drug delivery device. The drug delivery device is administered orally by a patient and then activated within the patient's Gastrointestinal (GI) tract. Upon actuation, the resilient arms within the drug delivery device expand and engage the wall of the gastrointestinal tract. The driver then drives a plunger within the drug delivery device, pushing the drug through a channel in the elastic arm and through the patient's gastrointestinal wall. After a period of time, at least a portion of the drug delivery device dissolves and the drug delivery device passes through the gastrointestinal tract.

Description

Oral drug delivery device with expansion arm

Technical Field

The present invention relates to an oral drug delivery device. More particularly, the present disclosure relates to an oral drug delivery device with an expansion arm that is activated in the small intestine to deliver a drug through the gastrointestinal wall.

Background

For patients undergoing treatment with drugs or some other biologically active compound, oral administration of the compound is often most convenient. However, the nature of some compounds is such that they cannot retain their activity once consumed. For example, some compounds, once placed in the environment of the Gastrointestinal (GI) system, denature, digest, or inactivate. In addition, the rate at which some compounds diffuse from the gastrointestinal system into the blood stream is low, which may prevent adequate dosage from being delivered to the patient. For compounds having these characteristics, the patient typically receives the compound by injection, which is painful and inconvenient. Accordingly, there is a need to develop an oral drug delivery device that can successfully deliver drugs that are ineffective when administered orally.

Disclosure of Invention

The present invention provides a drug delivery device. The drug delivery device is administered orally by the patient and then activated within the patient's digestive/Gastrointestinal (GI) tract. Upon actuation, the arms within the drug delivery device expand and penetrate the tip penetration (gastrointestinal) tract. The driver then drives a plunger within the drug delivery device, pushing the drug through the penetration tip and the gastrointestinal tract wall of the patient. After a period of time, at least a portion of the drug delivery device dissolves and the drug delivery device passes through the gastrointestinal tract.

In one exemplary embodiment, a drug delivery device is disclosed comprising a capsule configured to degrade within the Gastrointestinal (GI) tract of a patient; a drug delivery mechanism within the capsule and configured to interact with a gastrointestinal tract wall of a patient, the drug delivery mechanism comprising a plurality of resilient arms, a plurality of gastrointestinal tract wall interfacing/connecting/contacting ends, and a plurality of drug delivery channels, wherein the plurality of gastrointestinal tract wall interfacing ends are fluidly coupled with the plurality of drug delivery channels; a drug housing fluidly coupled to the drug delivery mechanism and configured to contain a volume of drug/a drug quantity; and a drive mechanism coupled to the drug housing, the drive mechanism including a stopper/occlusion, a trigger, and a driver, wherein the drive mechanism actuates delivery of the drug by the drug delivery mechanism.

In another embodiment, a drug delivery device is disclosed comprising a degradable capsule; a drug delivery mechanism within the degradable capsule comprising a fluid channel and a plurality of drug delivery members; a drug housing fluidly coupled to the fluid channel, configured to hold a volume of a drug; and a drive mechanism coupled to and at least partially within the drug housing, the drive mechanism including a drug housing cap configured to fluidly seal the drug housing; a drive rod slidable within the drug housing; a drive stop coupled to the drive rod configured to interface with the medicament; a driver located within the drug housing cap and coupled to the drive rod; the dissolvable trigger is configured to hold the drive rod in a first position, wherein when the dissolvable trigger degrades, the driver pushes the drive rod from the first position to the second position, and when the drive rod moves from the first position to the second position, the drug is released by the drug delivery mechanism.

In yet another embodiment, an oral drug delivery device is disclosed comprising a housing capsule; a drug delivery mechanism within the shell capsule comprising at least one drug delivery member configured to interact with a gastrointestinal wall of a patient; a fluid channel within the at least one drug delivery member configured to allow a drug to flow through the drug delivery member, wherein a fluid resistance within the fluid channel is greater than a interstitial resistance from interaction with a wall of the gastrointestinal tract; a drug housing coupled to the drug delivery mechanism; and a drive mechanism configured to drive the drug from the drug housing to the drug delivery mechanism.

In yet another embodiment, an oral drug delivery device is disclosed that includes a biodegradable capsule, a plurality of arms, and a liquid drug, wherein the oral drug delivery device has a closed configuration in which the plurality of arms are disposed within the capsule, an open configuration in which the plurality of arms extend radially outward to contact a patient when the capsule is degraded, a delivery configuration in which the liquid drug is injected into the patient through the plurality of arms, and a release configuration in which the plurality of arms are separated from the patient to pass through the patient.

Drawings

The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and the invention itself will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, wherein:

FIG. 1 is a perspective view of an exemplary embodiment of a drug delivery device according to the present disclosure;

fig. 2 is an exploded perspective view of the drug delivery device shown in fig. 1;

FIG. 3 is a right side view of the drug delivery device of FIG. 1;

FIG. 4 is a right cross-sectional view of the drug delivery device of FIG. 1;

FIG. 5 is a front view of the drug delivery device of FIG. 1;

FIG. 6 is a rear view of the drug delivery device of FIG. 1;

FIG. 7 is a perspective view of the drug delivery device of FIG. 1 in a closed position;

FIG. 8 is a perspective view of the drug delivery device of FIG. 7 in an open position;

FIG. 9 is a left side view of the drug delivery device of FIG. 1 in an open configuration within the patient's gastrointestinal tract, with the drive mechanism in a loaded position;

FIG. 10 is a side view of the drug delivery device of FIG. 9 with the drive mechanism in a delivery position;

FIG. 11 is an elevation view of the drug delivery device of FIG. 1 in an open state, delivering a drug to the gastrointestinal tract of a patient;

fig. 12 is a partially exploded view of a drug delivery member of the drug delivery device shown in fig. 1;

FIG. 13 is a partially exploded view of a drug delivery mechanism of the drug delivery device of FIG. 1;

figures 14-15 are partial exploded views of the gastrointestinal wall penetrating system of the drug delivery device of figure 1;

FIGS. 16-21 are simplified cross-sectional views of the device of FIG. 1 with an alternative seal assembly;

FIG. 22 is a perspective view of a trigger of the drug delivery device of FIG. 1;

FIG. 23 is an exemplary timeline of degradation of the device shown in FIG. 1;

FIG. 24 is a perspective view of an assembly mechanism for the drug delivery device shown in FIG. 1;

FIGS. 25-26 are a cross-sectional view and a partial cross-sectional view, respectively, of the assembly mechanism of FIG. 12;

FIG. 27 is a partially exploded view of several of the internal components of the assembly mechanism shown in FIG. 12; and

fig. 28-32 depict a method of assembling the drug delivery device of fig. 1.

Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the invention, and such exemplifications are not to be construed as limiting the scope of the invention in any manner.

Detailed Description

Referring first to fig. 1-6, a drug delivery device 100 is shown. Drug delivery device 100 comprises a capsule 110, a delivery mechanism 200, a drive mechanism 300 and a drug housing 400. The drug housing 400 may also be referred to as a cartridge. When the drug delivery device 100 is fully assembled, the capsule 110 encapsulates the delivery mechanism 200, the drive mechanism 300 and the drug housing 400. As discussed in more detail herein, the drug delivery device 100 is configured to be orally administered by a patient. Upon entering a portion of the patient's Gastrointestinal (GI) tract, capsule 110 degrades or otherwise ruptures, allowing delivery mechanism 200 to interact with the inner wall of the GI tract and secure drug delivery device 100 in place. Once the delivery mechanism 200 has interacted with the patient's gastrointestinal tract, the drive mechanism 300 actuates the delivery of the drug 500 from the drug housing 400 through the wall of the gastrointestinal tract to the patient. Once the drug 500 has been delivered, the drug delivery device 100 passes through the gastrointestinal tract.

As shown in fig. 2, the capsule 110 is composed of two parts, a first rear capsule part 104 and a second front capsule part 106. As discussed in more detail herein, the first capsule portion 104 and the second capsule portion 106 are coupled together to form a capsule 110.

When drug delivery device 100 is assembled, delivery mechanism 200 is configured to fit within capsule 110. In the illustrated embodiment, the delivery mechanism 200 includes a delivery base 230, a plurality of delivery members 210 extending from the delivery base 230, a membrane 220, and a central aperture 250 extending through the delivery base 230. Each delivery member 210 includes a resilient arm 215, a delivery channel 213, a docking end 217, and a penetrating assembly 260. In the illustrated embodiment, three delivery members 210 extend from the delivery base 230 and are equally spaced circumferentially around the delivery base 230, although in other embodiments any number of delivery members 210 and spacing arrangements may be used.

The delivery mechanism 200 is configured to allow fluid to flow from the central bore 250 through the delivery channel 213 to the docking end 217. The delivery channel 213 is fluidly coupled to the central bore 250 and extends along the resilient arm 215. In the illustrated embodiment, the transport channel 213 is formed as an exposed groove in the outer surface of the resilient arm 215. Referring to fig. 12, a film 220 is adhered to a surface of the elastic arm 215 to close and seal the transfer passage 213. The membrane 220 may be attached to the surface of the flexible arm 215 by adhesive, welding (heat, ultraviolet, laser, ultrasonic, solvent, friction, injection, high frequency, etc. type/manner of welding), mechanical connection, or any other connection means. The use of the membrane 220 may simplify the formation (e.g., molding, cutting) of the channels 213 in the outer surface of the resilient arms 215. In other embodiments, the delivery channel 213 may be a separate component (e.g., a tube) coupled to a portion of the delivery mechanism 200. Further, the transport channel 213 may be entirely located within the resilient arm 215 such that the interior of the transport channel 213 is entirely enclosed (e.g., through a hole of the resilient arm 215).

Referring to the illustrative embodiment of fig. 14-15, a docking end 217 is located near the end of each spring arm 215 and is configured to dock with the interior of the patient's gastrointestinal tract. Docking end 217 includes a socket 267 configured to receive penetrator assembly 260. Penetration assembly 260 includes a penetration piece base 264 and a penetration tip 266. As shown in fig. 14, in one embodiment, penetrating tip 266 is separate from penetrating member base 264, and penetrating member base 264 includes a receiving aperture 265, which receiving aperture 265 is configured to couple penetrating member base 264 to penetrating tip 266. In another embodiment, as shown in FIG. 15, penetrator base 264 and penetrator tip 266 may be formed as a single piece. The sockets 267 are configured to fluidly couple each of the delivery channels 213 to a corresponding penetrating tip 266 such that fluid may flow from the delivery channels 213 to the penetrating tip 266. At least one of the penetrator base 264 and the penetrating tip 266 may be biodegradable. In an exemplary embodiment, the abutment 217 interacts with an inner wall of the gastrointestinal tract and is generally parallel to the longitudinal axis A1, and the penetrating tip 266 pierces (pierce) or penetrates the wall of the gastrointestinal tract and is generally perpendicular to the axis A1. After a predetermined time has elapsed, the penetrator base 264 and/or the penetrator tip 266 may be degraded and released from the gastrointestinal tract. In the illustrated embodiment, the penetrating tip 266 has the shape of a hypodermic needle. In other embodiments, the penetrating tip 266 may include a piercing tip having a fluid outlet located below the penetrating tip (e.g., in a side surface of the penetrating tip 266) to avoid clogging in the delivery of the drug 500. Further, each delivery member 210 can include any number of penetrating tips 266, including microneedle arrays.

In an alternative embodiment, docking end 217 includes a liquid injector delivery mechanism for delivering fluid through the gastrointestinal tract. In this embodiment, the penetration assembly 260 (e.g., element 265) is formed as a nozzle or eductor that delivers fluid from the delivery channel 213 at high velocity to puncture and penetrate the gastrointestinal tract without using the penetration tip 266 to deliver the drug. In this embodiment, the drive mechanism 300, including the driver 360 described herein, actuates delivery of the medicament 500 from the medicament housing 400 with a high force adapted to drive a liquid jet.

Referring again to fig. 1-6, in the illustrated embodiment, the delivery base 230 and the delivery member 210 of the delivery mechanism 200 are a single, unitary piece. In the illustrated embodiment, the delivery member 210 and the delivery base 230 are resilient, having rigid, spring-like properties, wherein the delivery member 210 is adapted to flex relative to the base 230, as described herein. In an exemplary embodiment, the delivery mechanism 200 is adapted to dissolve or biodegrade in the intestine after delivery of the fluid. In an exemplary embodiment, the delivery mechanism 200 is composed of a polymer, such as a bioabsorbable/biodegradable polymer. Exemplary polymers include polyglycolic acid, polylactic acid, polycaprolactone, and copolymers and mixtures thereof, which may include polyethylene glycol. In other embodiments, the delivery mechanism 200 may be constructed of metal or other suitable material. As shown in fig. 13, the delivery mechanism 200 may alternatively be constructed of multiple sections connected by one or more coupling members 270. In the embodiment shown in fig. 13, a coupling member 270 couples the plurality of delivery members 210 together at the delivery base 230. Further, in the illustrated embodiment, the coupling member 270 is an i-shaped connector. In other embodiments, the coupling member 270 may be a fastener, screw, snap, pin, staple, or any other mechanical coupling. The coupling member 270 may be constructed of a biodegradable material, including the bioabsorbable/biodegradable polymers described above, such that the delivery mechanism 200 breaks into separate portions when the coupling member 270 degrades. The delivery member 210 and the coupling member 270 may both be composed of biodegradable materials, or only one of the delivery member 210 and the coupling member 270 may be composed of biodegradable materials. In other embodiments, any of the components of the delivery mechanism 200 may be manufactured as a single piece and coupled together by the coupling member 270. Further, the components of the delivery mechanism 200 may be coupled together by adhesive, welding, or other coupling means.

Referring again to fig. 1-6, the drug housing 400 is configured to be fluidly coupled to the delivery mechanism 200 via a housing coupling 450. The drug housing 400 is further configured to hold a volume of drug 500, typically in a liquid or other flowable form. In an exemplary embodiment, the drug 500 is a compound, such as a peptide or protein, such as insulin, that generally has less efficacy when administered by standard oral delivery and digestion. In one illustrative embodiment, the drug 500 includes one or more therapeutic agents including, but not limited to, insulin analogs such as insulin lispro or insulin glargine, insulin derivatives, GLP-1 receptor agonists such as delavay or liraglutide, glucagon analogs, glucagon derivatives, gastric Inhibitory Polypeptide (GIP), GIP analogs, GIP derivatives, combined GIP/GLP-1 agonists such as tepa peptide, oxyntomodulin analogs, oxyntomodulin derivatives, therapeutic antibodies, and other suitable therapeutic agents. Drug 500 may also include a vaccine or gene-based drug. In other embodiments, the drug 500 may be any biologically active compound to be administered to a patient. The drug housing 400 may be constructed of a polymer, metal, ceramic, crystalline solid, or any other material capable of containing the volume of drug 500.

Referring to fig. 16-21, in an alternative embodiment of the drug delivery device 100, a seal assembly may be used between the drug housing 400 and the delivery mechanism 200 to sealingly retain the drug 500 within the drug housing 400 until the drug 500 is ready to be introduced into the delivery mechanism 200. Referring first to fig. 16-17, in one embodiment, the drug housing 400 may include a septum 420 configured to be pierced by a needle 415, similar to configurations commonly used with automatic injection systems known in the art. During a priming step of the drug delivery device 100, for example when the drug delivery device 100 is assembled as shown in fig. 28-32, the needle 415 may be driven to pierce the septum 420. After the drug delivery device 100 has been ingested by the patient, the needle 415 may also be driven through the septum 420. For example, needle 415 may be driven by degradation of capsule 110, or by inclusion of additional degradable or force providing components (not shown) that may drive needle 415 upon degradation. In the illustrated embodiment, the membrane 420 is elastic and is coupled to the drug housing 400 by over-molding. In other embodiments, septum 420 may be constructed of any material suitable for retaining drug 500 within drug housing 400 and capable of being pierced by needle 415. Upon piercing septum 420 with needle 415, the interior of drug housing 400 is fluidly coupled to delivery mechanism 200 via connecting channel 450, allowing drug 500 to flow into delivery mechanism 200.

In the illustrated embodiment, the delivery mechanism 200 includes a housing sleeve 233 coupled to the delivery base 230 and configured to couple the delivery mechanism 200 to the housing 400. The housing sleeve 233 may be a sleeve that fits completely around the housing 400 or may comprise several discrete components. The housing sleeve 233 may also include a retention feature 231. The retention features 231 may be ridges, protrusions, grooves, or other means for retaining the housing sleeve 233 on the housing 400. The housing 400 may also include complementary features that interface with the retention features 231. In addition, an adhesive or other form of bonding agent may be applied to the housing sleeve 233 and/or the housing 400 to help retain the housing sleeve 233 around the housing 400.

Referring now to fig. 18-19, in another embodiment, housing 400 may include a rupturable membrane 430 at one end of connecting channel 450. Rupturable membrane 430 is configured to retain drug 500 within drug housing 400 until an increase in pressure causes rupturable membrane 430 to rupture or otherwise permit drug 500 to pass through connecting channel 450. The increase in pressure may be caused by actuation of the plunger 340. In the illustrated embodiment, the housing 400 interfaces with the delivery base 230 at a housing interface/interface 425. The housing interface 425 is configured to contact the delivery base 230 when the housing sleeve 233 engages the housing 400. The housing interface 425 may be coated with an adhesive or other bonding agent to help couple the housing 400 to the delivery mechanism 200. The housing interface 425 may also include surface features such as ridges, bumps, grooves, or other retention features for interfacing with the delivery base 230. In such embodiments, the delivery base 230 may include complementary surface features.

Referring to fig. 20-21, in yet another embodiment, the housing 400 may be molded closed to form an intentionally created weak point 440. The weak point 440 may rupture in a similar manner to the rupturable membrane 430 described above to allow the drug 500 to pass through the housing coupling 450. Embodiments including rupturable membrane 430 and/or weak spot 440 may not require the actuation or activation steps required for the needle 415 and septum 420 configurations shown in fig. 16-17.

The drive mechanism 300 is configured to be mounted at least partially within the drug housing 400 and is further configured to actuate the flow of drug 500 from the drug housing 400 into the delivery mechanism 200. The drive mechanism 300 includes a stopper 310, a plunger 340, a cap 330, a driver 360, and a trigger 350, and is disposed generally coaxially with the longitudinal axis A1. The cap 330 seals the medicament 500 within the medicament housing 400 and at least partially encloses the driver 360. The plunger 340 includes a stopper end 342 adjacent the stopper 310 and a trigger end 344 adjacent the trigger 350 and is movable from a first loading position to a second delivery position generally along the axis A1. At a stopper end 342 of the plunger 340, the plunger 340 is coupled to the stopper 310. In another embodiment, the plunger 340 is not coupled with the stopper 310. In the illustrated embodiment, the stopper 310 is separate from the drive mechanism 300 and may be inserted into the drug housing 400 before the drive mechanism 300 is coupled to the drug housing 400. This separation will allow the drive mechanism 300 without the stopper 310 to be assembled or manufactured separately from the drug housing 400 and the stopper 310 so that the drive mechanism may be later coupled to the drug housing 400.

Referring next to fig. 9-10, the stopper 310 is configured to seal the medication 500 within the medication housing 400 and is slidable generally along the axis A1. In the first loading position (see fig. 9), the trigger 350 is disposed between the trigger end 344 and the cap 330, thereby preventing the trigger end 344 from passing through the cap 330 and further preventing movement of the plunger 340. In the first loaded position, the driver 360 applies a force to the stopper end 342 generally toward the housing coupling 450. In the illustrated embodiment, the trigger 350 is constructed of a degradable material and is configured to degrade over time. When the trigger 350 is degraded and removed from its disposition between the trigger end 344 and the cap 330, the force applied to the plunger 340 by the driver 360 moves the plunger 340 generally along the axis A1 to a second delivery position (see fig. 10). During movement from the first position to the second position, the plunger 340 and stopper 310 move generally toward the housing coupling 450, thereby reducing the available volume of the drug housing 400 and pushing the drug 500 out of the drug housing 400 into the delivery mechanism 200.

In the illustrated embodiment, the driver 360 is a spring. In other embodiments, the driver 360 may be any member capable of transmitting a force to move the plunger 340 from the first position to the second position, including a balloon, piston, or motor. In the illustrated embodiment, due to the presence of the cap 330, the stopper 310, the plunger 340 and the driver 360 remain within the drug housing 400 after the drug delivery device 100 has been actuated and the drug 500 has been delivered. In this embodiment, accommodating a substantial portion of the drive mechanism 300 within the drug housing 400 prevents additional, potentially harmful components from being released into the gastrointestinal tract, but rather retains the components within the relatively smooth drug housing 400, which drug housing 400 will ultimately be passed by the patient.

Referring now to fig. 22, trigger 350 includes an interior 352, an interior edge 353, an upper surface 354, and at least one chamfer 355. The chamfer 355 may also be located at other points along the inner edge 353 and may even extend completely around the inner edge 353. Further, the upper surface 354 may slope downward toward the interior 352 on a portion or all of the trigger 350. The plunger 340 is configured to fit within an interior 352 of the trigger 350. The ramp 355, along with the generally horseshoe shape of the trigger 350, is configured to direct force from the driver 360 through the trigger end 344 of the plunger 340 onto a smaller area of the trigger 350. Thus, the trigger 350 is configured to fracture more easily than if the trigger 350 were a solid disk. In addition, since many biodegradable materials do not dissolve completely in a short period of time, the shape of the trigger 350 and the ramp 355 causes the trigger 350 to snap or fracture and fail abruptly after a threshold level of degradation has occurred. This configuration allows the drive mechanism 300 to be actuated in a relatively quick manner once the trigger 350 degrades beyond a threshold amount.

Referring to fig. 7-8, the drug delivery device 100 is movable from a first state or closed state (see fig. 7) to a second state or open state (see fig. 8). The delivery member 210 of the delivery mechanism 200 is constructed of an elastic material, such as a polymer having flexible, rigid and spring-like properties. In the illustrated embodiment, when no force is acting on the conveying members 210, their natural state is an open state. However, the delivery member 210 can move to the closed state and then can spring back or expand back to the second state due to the resiliency of the delivery member 210. In the closed condition, the delivery member 210 is contained within the capsule 110, substantially parallel to the axis A1 (see fig. 7). In the closed state, the delivery member 210 applies a radially outward force inside the capsule 110. When the capsule 110 degrades, dissolves, or otherwise breaks beyond a predetermined point, the delivery member 210 may break through any remaining capsules 110 and move radially outward from the axis A1 to enter an open state (see fig. 8).

When the drug delivery device 100 is used to treat a patient, the patient orally administers the drug delivery device 100 and the drug delivery device 100 passes through the patient's gastrointestinal tract. In an exemplary embodiment, the capsule 110 degrades when the environment surrounding the drug delivery device 100 changes pH, for example, when exiting the acid stomach and entering the relatively alkaline small intestine. When the capsule 110 degrades beyond the threshold amount of the predetermined point described above, the drug delivery mechanism 200 breaks through the capsule 110 and the delivery member 210 extends outwardly. Within the patient's gastrointestinal tract, as delivery member 210 is extended outwardly, docking end 217 interfaces with the interior of the patient's gastrointestinal tract, also referred to as gastrointestinal tract wall 700. The penetrating tip 266 penetrates the gastrointestinal tract wall 700, thereby anchoring the drug delivery device 100 to the wall 700 at the penetration point (see fig. 9). The abutment end 217 is configured to abut the wall surface 710 when the penetrating tip 266 penetrates the wall 700. In embodiments using liquid jet delivery, the spring force of the delivery member 210 against the wall 700 may be configured to provide sufficient anchoring force to deliver the drug. Additionally or alternatively, the end 217 may include a docking feature, such as a penetrating tip or ridge, for grasping and anchoring the device 100 to the wall 700 during delivery of the liquid jet.

After the drug delivery device 100 penetrates the gastrointestinal tract wall 700, the trigger 350 degrades beyond a threshold value, allowing the driver 360 to drive the plunger 340 and stopper 310 into the drug housing 400, pushing the drug 500 through the delivery mechanism 200 (see fig. 10) and into the wall 700 through the penetrating tip 266 (see fig. 11). After the drug 500 has been delivered to the patient through the penetrating tip 266, the penetrating assembly 260 will degrade. Upon degradation of penetration assembly 260 beyond a threshold, delivery mechanism 200 will rupture or release from penetration assembly 260 and will traverse the gastrointestinal tract. As described above, other components of the delivery mechanism 200 may also break when the coupling member 270 degrades. In some embodiments, components of delivery mechanism 200 made of biodegradable/bioabsorbable polymers (described herein) are also adapted to degrade and dissolve after drug delivery.

Referring to fig. 23, a depiction of the relative degradation times of the different components of the drug delivery device 100 is shown, according to one exemplary embodiment. In the illustrated embodiment, the first degraded component is capsule 110, exposing the internal components of device 100 and allowing device 100 to spring open and position itself within the gastrointestinal tract. The next component to degrade is the trigger 350, which activates the delivery mechanism 300 and delivers the drug 500 to the patient. The next component to degrade is the delivery member 210 and/or the coupling member 270, allowing the drug delivery device 100 to pass through the remainder of the gastrointestinal tract and be passed by the patient. Finally, penetrator assembly 260 or certain components within penetrator assembly 260 degrade. Both capsule 110 and trigger 350 degrade in the range of about a few minutes or seconds. Delivery member 210 and/or coupling member 270 degrade in the range of about a few hours. Penetration assembly 260 or a component thereof degrades in about a few hours or days. In other embodiments, the components of the drug delivery device 100 may be designed to degrade on other suitable time scales.

In the exemplary embodiment, delivery mechanism 200 includes a pressure regulator (not shown). When the penetrating tip 266 penetrates the gastrointestinal wall 700, interstitial/interstitial pressure is created at the wall surface 710. In order for the drug 500 to pass through the gastrointestinal wall surface 710, the driver 360 must create a pressure within the drug 500 that is greater than the interstitial pressure so that the drug 500 flows through the wall 700. The pressure regulator sets a pressure threshold that is greater than the pressure of the medium in each delivery member 210 such that the driver 360 must generate a pressure within the drug 500 that is greater than the pressure threshold such that the drug 500 flows through the delivery members 210. Thus, in the event that one or more of the penetrating tips 266 does not penetrate the wall 700, the disengaged penetrating tip 266 that does not penetrate the wall 700 will still be affected by the pressure threshold set by the pressure regulator, and thus a portion of the drug 500 will still be delivered through the engaged penetrating tip 266 that has penetrated the wall 700. Without a pressure regulator, most of the drug 500 would escape through the penetrating tip 266 that does not penetrate the wall 700, as they would provide a path of less resistance.

In another embodiment, only one delivery member 210 may contain the delivery channel 213, and thus only that one delivery member 210 may deliver the drug 500 to the patient. Other delivery members 210 may be configured to function as "virtual" or structural delivery members 210, and may be present to help secure drug delivery device 100 within the gastrointestinal tract, rather than as a means of delivering drug 500. The structural delivery member 210 may not include a penetrator assembly 260 because no drug 500 may flow through the delivery member 210 and then through the penetrator assembly 260. The structural delivery member 210 may include a docking feature (not shown) on the docking end 217 to grasp the gastrointestinal tract wall 700. Such interfacing features may include ridges, protrusions, adhesive, or other clamping/attachment means. The structural delivery member 210 can also include microneedles, patches, solid drug deposits, or other drug delivery means to allow diffusion of a drug or other active agent through the wall 700 without penetration.

24-27, to reduce the likelihood of viscoelastic creep within the delivery mechanism 200, a device assembly mechanism 800 is provided. In an exemplary embodiment, a user or patient may receive the device assembly mechanism 800 and assemble the drug delivery device 100 shortly before oral administration of the drug delivery device 100. The device assembly mechanism 800 includes an assembly housing 820, an assembly actuator 810, an access window 825, a rotating member 850, a first drive rod 840, a second closure rod 845, and a device retraction region 830. The assembly actuator 810 is configured to be pressed or otherwise activated by a user to trigger assembly of a single drug delivery device 100 at a time. In the illustrated embodiment, the device assembly mechanism 800 is loaded with a plurality of drug delivery devices 100. The first capsule portion 104 and the internal components of the drug delivery device 100 (in particular, the delivery mechanism 200, the drive mechanism 300, the drug housing 400 and the drug 500) are held in the rotary member 850 and the second capsule portion 106 is held in the actuator 810. In the illustrated embodiment, access window 825 may be removed to allow additional loading of device assembly mechanism 800. When the assembly actuator 810 is activated, the first drive rod 840 drives the internal components of the drug delivery device 100 into the first capsule portion 104. The first drive rod 840 also brings the second capsule portion 106 into contact with the first capsule portion 104. The second capsule portion 106 and the first capsule portion 104 may be coupled by friction, welding, adhesive, mechanical fasteners, or other coupling means. Once the capsule 110 is fully formed around the internal components of the drug delivery device 100, the second closure rod 845 releases the drug delivery device 100 from the rotational member 850 and brings the drug delivery device into the device retraction region 830. This process may be repeated before each drug delivery device 100 is orally administered to the patient.

28-32, an exemplary embodiment of a device assembly process is depicted. The drug housing 400 and the drive mechanism 300 are combined and simplified in the drug drive unit 900. The delivery mechanism 200 is pushed into the first capsule portion 104 and into a closed state wherein the delivery member 210 partially encapsulates the drug drive unit 900. The drug drive unit 900 is pushed further into the delivery mechanism 200 such that the drug drive unit 900 and the delivery mechanism are fluidly coupled. The second capsule portion 106 is then pushed onto the drug drive unit 900 and the delivery mechanism 200 and then sealed onto the first capsule portion 104.

In another embodiment, the drug delivery device 100 may include a wireless communication device configured to transmit and/or receive signals to/from a wireless receiver (not shown). The wireless communication device may be configured to measure or sense biological information in the patient after the drug delivery device 100 has been ingested. For example, the wireless receiver may send a signal when the delivery mechanism 200 has been inflated, or when a portion of the drug delivery device 100 has degraded. In addition, the wireless communication device may measure/sense other biological information within the gastrointestinal tract, such as chemical concentration, pH, temperature, or other biological information. The wireless receiver may be used by the patient receiving the treatment or by another user, such as a doctor or caregiver. The wireless communication device and the wireless receiver may communicate via RFID, magneto-acoustic, near field communication, ultrasound, bluetooth technology, or other wireless communication means.

While this invention has been described as having an exemplary design, the present invention may be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles. Furthermore, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.

Claims

1. A drug delivery device comprising:

a capsule configured to degrade within the gastrointestinal tract of a patient;

a drug delivery mechanism within the capsule configured to interact with a wall of a gastrointestinal tract of a patient, the drug delivery mechanism comprising a plurality of resilient arms, a plurality of wall interfacing ends, and a plurality of drug delivery channels, wherein the plurality of wall interfacing ends are fluidly coupled with the plurality of drug delivery channels;

a drug housing fluidly coupled to the drug delivery mechanism and configured to contain a volume of drug; and

a drive mechanism coupled to the drug housing, the drive mechanism including a stop, a trigger, and a driver located within the drug housing, wherein the drive mechanism actuates delivery of the drug by the drug delivery mechanism.

2. The drug delivery device of claim 1, wherein the capsule is configured to degrade upon entering the small intestine of the patient.

3. The drug delivery device of claim 1, wherein the drug delivery mechanism is configured to transition from the closed position to the open position after degradation of the capsule, wherein the drug delivery mechanism expands radially outward in the open position to interact with the gastrointestinal tract wall of the patient.

4. A drug delivery device as in claim 3, wherein the plurality of wall interfacing ends comprise a penetrating tip configured to penetrate a wall of the gastrointestinal tract when the drug delivery mechanism is in the open position.

5. A drug delivery device as in claim 3, wherein the plurality of wall interfacing ends comprise at least one liquid ejector configured to deliver the drug as a jet through the gastrointestinal tract wall.

6. A drug delivery device as in claim 3, wherein the trigger is dissolvable in the gastrointestinal tract of the patient and degrades after the drug delivery mechanism is in the open position, the drive mechanism being activated when the trigger degrades.

7. The drug delivery device of claim 1, wherein the wall abutment end comprises a penetrating tip that is a dissolvable needle structure configured to pierce a gastrointestinal wall of a patient and degrade within the gastrointestinal tract of the patient.

8. The drug delivery device of claim 1, wherein the resilient arms are coupled together by a plurality of dissolvable coupling members configured to degrade within the gastrointestinal tract of the patient.

9. The drug delivery device of claim 1, further comprising a channel membrane, wherein each channel of the plurality of drug delivery channels is formed within a respective elastic arm, the channel membrane separating an interior of the plurality of drug delivery channels from a gastrointestinal tract of a patient.

10. The drug delivery device of claim 1, further comprising a membrane within the drug housing, the membrane comprising a sealed configuration in which the membrane holds the drug within the drug housing and an open configuration in which the membrane at least partially opens and allows the drug to flow out of the drug housing.

11. The drug delivery device of claim 1, further comprising a cap coupled to the drug housing, wherein the cap prevents the drive mechanism from exiting the drug housing and entering the gastrointestinal tract.

12. The drug delivery device of claim 1, wherein at least one component of the drug delivery mechanism degrades upon actuation of the drug delivery by the drive mechanism.

13. The drug delivery device of claim 12, wherein the drug delivery mechanism further comprises a plurality of coupling members configured to degrade within the gastrointestinal tract.

14. The drug delivery device of claim 1, wherein the stopper is coupled to the drug housing separately from the driver and the trigger.

15. The drug delivery device of claim 1, wherein the drug delivery mechanism is comprised of a biodegradable polymer comprising at least one of polyglycolic acid, polylactic acid, and polycaprolactone.

16. The drug delivery device of claim 1, further comprising a drug contained within the drug housing, the drug comprising at least one of a peptide and a protein.

17. An assembly system for assembling the drug delivery device of claim 1, the assembly system comprising:

assembling a system housing;

an assembly actuator coupled to the housing and configured to be actuated by a user;

a rotating member within the housing configured to hold a first portion of the capsule;

a drive rod configured to drive the drive mechanism, the drug delivery mechanism and the drug housing at least partially within the first portion of the capsule when the assembly actuator is activated; and

a closure rod configured to couple the second portion of the capsule to the first portion of the capsule, thereby completely enclosing the drug delivery mechanism, the drug housing and the drive mechanism within the capsule.

18. A drug delivery device comprising:

degradable capsules;

a drug delivery mechanism within the degradable capsule comprising a fluid channel and a plurality of drug delivery members;

a drug housing fluidly coupled to the fluid channel, configured to hold a volume of a drug; and

a drive mechanism coupled to and at least partially within the drug housing, the drive mechanism comprising:

a drug housing cap configured to fluidly seal the drug housing;

a drive rod slidable within the drug housing;

a drive stop coupled to the drive rod configured to contact the drug;

a driver located within the drug housing cap and coupled to the drive rod;

a dissolvable trigger configured to hold the drive rod in the first position,

wherein the driver pushes the drive rod from the first position to the second position when the dissolvable trigger degrades and the drug is released by the drug delivery mechanism when the drive rod moves from the first position to the second position.

19. The drug delivery device of claim 18, wherein the degradable capsule is configured to degrade upon a change in pH in an environment surrounding the degradable capsule.

20. The drug delivery device of claim 18, wherein each of the plurality of drug delivery members comprises a resilient arm and a wall abutment end comprising at least one liquid ejector configured to deliver a drug as a jet through the gastrointestinal tract wall.

21. The drug delivery device of claim 18, wherein each of the plurality of drug delivery members comprises a resilient arm and a penetrating tip configured to penetrate a gastrointestinal wall of a patient's small intestine.

22. The drug delivery device of claim 21, wherein the penetrating tip comprises a needle and a degradable base, the degradable base coupled to the resilient arm, the needle coupled to the degradable base.

23. The drug delivery device of claim 21, wherein the penetrating tip comprises a degradable needle configured to degrade after penetrating a gastrointestinal wall of the small intestine of the patient.

24. The drug delivery device of claim 18, wherein the dissolvable trigger comprises a ramp configured to weaken the structure of the dissolvable trigger upon degradation of the dissolvable trigger.

25. The drug delivery device of claim 18, wherein the fluid channel is located within one of the drug delivery members and the remaining ones of the drug delivery members are structural drug delivery members configured to position the drug delivery device within the gastrointestinal tract of the patient.

26. An oral drug delivery device comprising:

a shell capsule;

a drug delivery mechanism within a shell capsule comprising:

at least one drug delivery member configured to interact with a Gastrointestinal (GI) wall of a patient;

a fluid channel within the at least one drug delivery member configured to allow a drug to flow through the drug delivery member, wherein the fluid resistance within the fluid channel is greater than interstitial resistance from interaction with the gastrointestinal wall;

a drug housing coupled to the drug delivery mechanism; and

a drive mechanism configured to drive the drug from the drug housing to the drug delivery mechanism.

27. The oral drug delivery device of claim 26, wherein the drug delivery mechanism is at least partially constructed of an elastic polymer and is configured to transition from a first position to a second position, the at least one drug delivery member being configured to interact with the wall when the drug delivery mechanism is in the second position.

28. A method of treatment with the oral drug delivery device of claim 26, comprising:

loading an unassembled oral drug delivery device into an assembly mechanism;

actuating an assembly mechanism configured to: inserting the drug delivery mechanism into the first portion of the housing capsule and coupling the second portion of the housing capsule to the first portion of the housing capsule;

receiving an oral drug delivery device from an assembly mechanism; and

an orally ingestible drug delivery device.

29. The oral drug delivery device of claim 26, wherein the drive mechanism comprises a dissolvable trigger configured to degrade upon at least partial removal of the drug delivery mechanism from the housing capsule.

30. The oral drug delivery device of claim 26, wherein the drug delivery mechanism is configured to expand and anchor the drug delivery mechanism within the wall of the gastrointestinal tract.

31. The oral drug delivery device of claim 26, further comprising a coupling channel between the drug housing and the delivery mechanism and a weak point within the coupling channel configured to fracture upon application of a threshold pressure to the weak point.

32. An oral drug delivery device comprising:

biodegradable capsules;

a plurality of arms; and

a liquid drug;

wherein the oral drug delivery device has:

a closed configuration in which the plurality of arms are disposed within the capsule;

an open configuration in which the plurality of arms extend radially outward to contact a patient upon degradation of the capsule;

a delivery configuration in which liquid medicament is injected into a patient through the plurality of arms; and

a released configuration in which the plurality of arms are separated from the patient to pass through the patient.

33. The oral drug delivery device of claim 32, further comprising a needle and a septum, wherein the oral drug delivery device has: (1) An unactuated configuration in which the needle does not contact the septum, and (2) an actuated configuration in which the needle pierces the septum.

34. The oral drug delivery device of claim 32, further comprising a trigger and a plunger within the capsule, and a ramp on the trigger, wherein the oral drug delivery device transitions to a delivery configuration after the trigger is at least partially degraded and the plunger moves past the ramp.

35. A method of delivering a drug to a patient by a drug delivery device, comprising:

orally administering a drug delivery device to a patient;

degrading the capsule in the small intestine of the patient;

after the degrading step, expanding a delivery mechanism having a plurality of ends to contact the small intestine of the patient;

engaging a small intestine wall of a patient with a penetrating assembly disposed at one end of a delivery mechanism;

degrading a trigger of the drug delivery device;

delivering a drug to a patient through a delivery mechanism; and

degrading the delivery mechanism.

36. The method of claim 35, wherein the penetration assembly comprises a liquid ejector configured to deliver the drug as a jet penetrating the wall of the small intestine.

37. The method of claim 35, wherein the engaging step comprises penetrating the small intestine of the patient with a plurality of penetrating tips disposed at the end of the delivery mechanism.

38. The method of claim 35, wherein the degrading step further comprises degrading the delivery mechanism.